Some mechanisms of local bone destruction by squamous carcinomas of the head and neck

Abstract

Summary.-An in vitro osteolysis assay with 45Ca-labelled mouse calvaria has been used to investigate mechanisms of direct bone invasion by squamous carcinomas of the head and neck. Short-term (3-day) organ cultures of 8 fresh squamous carcinomas showed varying degrees of in vitro bone-resorbing activity which was blocked by indomethacin, an inhibitor of prostaglandin synthesis. Supernatant media from 6 established cell lines also induced bone resorption in vitro and evoked an osteoclastic response in the cultured calvaria. Osteolysis by supernatant media was not blocked by indomethacin in all the tumour-cell lines, and the production of nonprostaglandin osteolysins by the indomethacin-resistant lines is postulated. The two principal findings that emerge are: (1) Stimulants for osteoclastic activity are derived from both squamous-carcinoma cells and from host cells in the tumour stroma.(2) These stimulants are diverse. Indomethacin-sensitive agents, presumed to be prostaglandins, are most convincingly demonstrated in the fresh tumours. Indomethacin-resistant agents, presumably not prostaglandins, are more characteristic of the carcinoma cell lines.

Ten human carcinoma cell lines derived from squamous carcinomas of the head and neck

“…Detailed clinicopathological studies of the patterns of spread of squamous carcinomas of the head and neck into perineural spaces, bone and cartilage, and to regional lymph nodes, have been reported Carter & Pittam, 1980;Tanner et al, 1980); current investigations are concerned with some of the underlying mechanisms, with particular respect to tumourassociated destruction of soft tissues and bone (Tsao et al, 1981). The information that can be obtained from examining fresh tumours is somewhat limited, and access to a number of continuous cell lines derived from squamous carcinomas of the head and neck would considerably facilitate investigations of the behaviour and properties of these tumours.…”

Macromolecular osteolytic factor synthesised by squamous carcinoma cell lines from the head and neck in vitro is interleukin 1

“…There is much evidence that prostaglandins are synthesised by human carcinomas (Bennett et al, 1975;Dowsett et al, 1976;Tsao et al, 1981Tsao et al, , 1983 and, in view of their potent bone resorbing activity, notably PGE2 (Klein & Raisz, 1970), they have been considered prime candidates as osteolytic mediators. The experiments reported by Tsao et al (1983) showed that although explanted tumour fragments synthesised amounts of PGE2 enough to account for the majority of bone resorption in vitro, the carcinoma cell lines synthesised little prostaglandins but significant prostaglandinindependent osteolytic factors.…”

“…The cell lines were established as described by Tsao et al (1981). Two of the squamous carcinoma cell lines (HNI1 and 15) were derived from the floor of the mouth and the third (HN12) from the hypopharynx.…”

“…PGs, however, are only one class of bone resorbing factor which may contribute to tumour osteolysis. Tsao et al (1981Tsao et al ( , 1983 showed that the bone resorption induced in culture by explants of squamous cell carcinoma of the head and neck was only partially inhibited by indomethacin. Indeed, carcinoma cell lines cultured from these tumours produced bone resorbing activity in the culture supernatants, but no detectable PGs.…”

“…Prostaglandins (PG), notably PGE2, have been considered prime candidates as local mediators of osteolysis since they are potent stimulators of oesteoclastic bone resorption (Klein & Raisz, 1970) and are synthesised in increased amounts by several tumours in animals, including fibrosarcoma in mice (Tashjian et al, 1972) the VX2 carcinoma in rabbits (Voelkel et al, 1975), and in man, including carcinoma of the breast (Bennett et al, 1975);Dowsett et al, 1976), and squamous carcinomas of the head and neck (Tsao et al, 1981). PGs, however, are only one class of bone resorbing factor which may contribute to tumour osteolysis.…”